Lab Comments
<dl = Unable to determine results due to less than detectable levels of analyte.
The performance characteristics of all assays have been verified by Genova Diagnostics, Inc. Unless otherwise noted with as cleared by the U.S. Food and Drug Administration, assays are For Research Use Only.
Commentary is provided to the practitioner for educational purposes, and should not be interpreted as diagnostic or treatment recommendations. Diagnosis and treatment decisions are the responsibility of the practitioner.
Reference Range Information
Elemental reference ranges were developed from a healthy population under non-provoked/non-challenged conditions. Provocation with challenge substances is expected to raise the urine level of some elements to varying degrees, often into the cautionary or TMPL range. The degree of elevation is dependent upon the element level present in the individual and the binding affinities of the challenge substance.
Lead
is above the reference range. 75% to 80% of absorbed lead is typically excreted via urine, 15 to 20% via bile, and the remainder via sweat, hair and nails. In non-provoked urine, lead levels can fluctuate according to variable dietary and physiological factors, and the level does not necessarily reflect body burden. Provoked levels, however, can be indicative of excess lead in body tissues. It is notable that for children (compared with adults), lead can be more toxic, with detrimental effects occurring at much lower levels. Furthermore, toxicity of lead can be significantly increased synergistically by the presence of either mercury or cadmium.
Most lead uptake occurs via ingestion of contaminated food or water. Inhalation of lead dusts and transdermal absorption of organic lead salts are other modes of uptake. While temporarily carried in the bloodstream, lead is at least 90% bound to erythrocytes, however, with chronic low-level or long-ago exposure, only 2% or less of total body lead remains in the blood. Lead primarily deposits and accumulates in the aorta, liver, kidneys, adrenal and thyroid glands, bones and teeth. This element interferes with membrane functions, bonds to sulfhydryl (-SH), phosphate, hydroxyl and amino sites on proteins and enzyme cofactors, and interferes with heme synthesis, iron transport, erythrocyte life span, and hepatic cytochrome P-450 functions. Other deleterious effects include: reduced vitamin D synthesis, slowed nerve conduction, peripheral neuropathy, hypertension (adults) and loss of IQ and developmental disorders (children). Anemia, neuropathies and encephalopathy are end-stage conditions of severe lead excess.
Although historic uses of lead (housepaint, anti-knock gasoline additives, and soldered joints in water systems) have been discontinued, old building materials, paint chips, plumbing and the environment may contain residual amounts from these sources. Other sources include batteries in cars, trucks, boats, and power backup systems, art supplies, colored glass kits, bullets, fishing sinkers, balance weights, radiation shields, bearing alloys, babbitt metal, some ceramic glazes or pigments, and sewage sludge. Some cities that have not replaced old water mains may have variable amounts of lead in the drinking water.
Mercury
is measured to be elevated. In body tissues, mercury behaves differently in different tissues, depending on its chemical form, and interchange between forms can occur in vivo. For elemental and inorganic mercury, biliary excretion predominates with low-level toxicity, but urinary excretion increases and is favored as the degree of exposure and burden increases. For organic mercury (methyl, ethyl, alkyl), bile accounts for about 90% of excretion and urine accounts for about 10%. Significant day-to-day and diurnal variations are typically observed. Urinary excretion of mercury is notably increased following administration of chelating or detoxifying agents (DMSA, DMPS); intravenous administration of EDTA results in relatively minor urinary increases. The GSDL laboratory procedure measures total urine mercury, regardless of chemical form, and the procedure is not hindered by tightly-bound sulfhydryl-mercury that might be unavailable (and unmeasured) by the old standard procedure ("cold-vapor atomic absorption").
There is great variability in individual tolerances to mercury. In some individuals, relatively low levels can cause immune dysregulation. Lymphocyte inhibition and dysfunction is reported, immunosupression can occur, and autoimmune conditions are documented in animals. At the cellular level, mercury can induce cytotoxicity, oxidative stress (via loss of glutathione function), and increased secretion of beta-amyloid in neuronal cells, linking it to Alzheimer's disease. Outside cells, mercury can bind to and strongly inhibit a cell surface-bound protein called dipeptidylpeptidase IV, CD26, and adenosine deaminase binding protein. This one protein is responsible for digestion of proline-containing dietary peptides, T-cell activation, and the metabolism of adenosine. Inside cells, mercury binds to lipoic acid, glutathione, coenzyme A and cysteinyl sites, and it can impair pyruvate metabolism and citric acid (Kreb's) cycle function, leading to impaired energy production. Chronic mercury exposure may produce increased excitability and tremor, memory loss, insomnia, lassitude, anorexia and weight loss, gingivitis and stomatitis. Young children may exhibit "pink disease" (acrodynia), commonly featuring rash, photophobia, increased perspiration and salivation. Acute mercury vapor exposure may inflame the bronchial tubes and cause pneumonitis. Irreversible neurologic damage is reported in acute mercury toxicity. Inorganic mercury concentrates mostly in kidneys, while organic (methyl) mercury has high affinity for the posterior cortex of the brain.
Mercury sources have increased in the environment, resulting in increased amounts in soils, sediments and bodies of water. Coal-fired power plants emit over 30% of environmentally released mercury. Other industrial sources are chlorine or "chlor-alkali" plants, cement plants, pulp and paper mills, municipal waste incinerators (19% of total release), and hazardous/medical waste incinerators. As of 2001, over 100 tons of mercury are "missing" from the EPA-surveyed inventory of chlor-alkali plants which admit to releasing the element to air and landfills. These sources, along with increased farming, forest fires, mining and excavations, and volcanoes, have served to increase surface deposition (micrograms per square meter) of mercury in surveyed areas by over 300% since 1850. This mercury can be biologically changed into organic forms and made bioavailable. Fish, shellfish and edible seaweed then become dietary sources of this element. Other sources include: old latex paint (manufactured before 1990), antifungal and antifouling (marine) paints, some fluorescent light tubes and vapor lamps, medicinal products such as those containing "Thimerosal" (sodium ethyl mercurithiosalicylate or mercurothiolate--often contained in routine vaccines), explosives and detonators, batteries and "calomel" electrodes, electrical switches, thermostats and relays, and scientific or laboratory equipment (thermometers, barometers). Dental amalgams are primarily a source of elemental or amalgamated mercury that is typically found in feces for several days following dental procedures; very little of this dental-procedure mercury appears in urine. However, mercury vapor from in-place amalgam fillings can be absorbed, biotransformed and excreted in urine, but its level is typically much less than that which is attributable to food sources, especially seafood.
Antimony
is above the reference range. This element can have two oxidation states, Sb(+3) and Sb(+5). These forms follow different paths of tissue deposition and excretion. Both forms are found in urine; the amounts depend upon the elapsed time from exposure. Typically Sb(+5) predominates with lesser amounts of Sb(+3) (the opposite trend occurs in bile and fecal matter). However, this trend is time-dependent in degree with considerable Sb(+3) being excreted via urine for several days after the exposure. Therefore, research reports and toxicology texts differ with respect to describing excretion routes of Sb(+3) and Sb(+5).
Symptoms associated with low level or chronic Sb contamination may have delayed or insidious onset and can depend upon the chemical form. Sb rapidly clears the blood (typically within two hours of a point-in-time exposure) and accumulates in the adrenals, thyroid, kidney, liver, spleen, and bone. The Sb(+3) that is not promptly excreted (urine) is preferentially distributed in the liver and is primarily excreted via bile and feces. Sb(+5), if not excreted via the kidneys in urine, can deposit in bone. Antimony interferes with cellular metabolism by combining with sulfhydryl groups (-SH) on enzymes. Antimony may also disrupt purine metabolism, leading to elevated uric acid, ammonia, inosine or hypoxanthine. By inhibiting the enzyme, monoamine oxidase (MAO), the element can disrupt adrenal catecholamine metabolism. Signs and symptoms consistent with chronic antimony toxicity are variable and may include metallic taste, anorexia, fatigue, myopathy, gout-like symptoms, MAO dysfunction, hypotension, erythrocyte fragility, and angina. "Antimony spots" may result from skin contact with antimony compounds; inhalation of antimony may result in nosebleeds, rhinitis, and pneumonitis.
Sources of antimony include solders, metal type (printing), antifriction alloys (bearings, babbitt metal), small-arms ammunition, lead batteries, paints, enamels, glass and pottery glazes, flame-proofing/retardants for textiles and carpets, mordants for textiles and leather dyes, vulcanizing and coloring agent for rubber, tobacco, mines and smelting operations.
Copper
is above the reference range. An essential element, some small excretion of copper occurs via urine; most copper (98%) is normally excreted via bile/feces. Biliary insufficiency, cirrhosis or liver disease with cholestasis can decrease biliary copper excretion and increase urinary amounts. Administration of sulfhydryl (-SH)-bearing chelating or detoxifying agents, especially "Cuprimine" (D-penicillamine) can greatly increase urinary copper levels. In Wilson's disease, a rare but notorious condition of copper loading in body organs, urinary copper excretion is increased by factors of 3 to 25.
Conditions that may result from excess copper include abnormal renal transport, glucosuria, hyperaminoaciduria, tremor, dementia, hemolytic anemia, jaundice, hypotension, reduced blood level of vitamin A, and molybdenum deficiency.
Contamination of body tissues with toxic excesses of copper is infrequent; biliary dysfunction or liver disease is a more common reason for urinary copper excess. Chlorination of drinking water has about doubled its copper content, and for the 100 largest US cities, drinking water varies from 1 to 250 μg/l. Copper is present in electrical systems, brass and bronze alloys, anti-fouling paints, pigments, algicides and fungicides. Smelting and refining operations can produce fumes and "metal fume fever" which includes copper toxicity. By far, the most likely cause for excess copper intake is drinking acidic water that has passed through copper plumbing.
Iron
(Fe) is above the reference range in urine. Excess ingested iron is excreted in stool, bile and urine. An indication of excess total body iron load, increased urinary iron excretion should be evaluated for indications of 'iron overload'. Evaluation of iron storage problems is evaluated with a serum ferritin assay. Hemochromatosis should be considered. Iron overload can cause disturbances in the liver and pancreas, as well as lipid peroxidation, endocrine effects and cardiovascular disease. Treatment of iron overload is with repeated phlebotomy, though desferrioxamine is the chelating agent of choice for acute iron toxicity.
Gadolinium
(Gd) is above the reference range in urine. Gadolinium is a member of a group of rare earth metals known as lanthanides. It has been used for superconductors, magnets, fluorescent materials, and as a nuclear MRI contrast agent. Toxicity appears similar to nickel and copper, and has been associated with hair loss and skin lesions. These changes are consistent with Zinc deficiency and are correlated with increased urinary zinc concentrations.
Manganese
is above the reference range. Biliary dysfunction and administration of chelating agents, especially EDTA and, to a lesser extent, D-penicillamine, can result in increased or elevated urine manganese.
At physiological levels, manganese is an essential element that functions as an activator of certain enzymes. In excess, this element can accumulate in cell mitochondria in the pancreas, liver, kidneys, and intestines, and also deposits in bone and in the brain. In the nervous system, manganese decreases dopamine and its function. Emotional instability, compulsive and aberrant behaviors are also attributed to excess manganese.
Manganese is used in the manufacture of steel and bronze alloys, batteries, electronic components, water conditioning systems (potassium permanganate for high-iron water), matches, welding rods, glazes, dyes and pigments.
Nickel
is above the reference range. Up to 90% of absorbed nickel is excreted via urine; sweat and bile/feces account for the remainder. Administration of sulfhydryl agents (D-Penicillamine, DMPS) can mobilize sequestered nickel and increase its concentration in urine. Besides food, cigarettes are a common source of bioavailable nickel. Usually, excretion of nickel is rapid being nearly completely released in five days.
Inhaled nickel, especially nickel carbonyl, is a respiratory tract carcinogen, producing squamous cell carcinomas. Nickel typically distributes to bone, lung, liver, kidney, intestinal mucosa, and skin. At low concentrations, nickel induces heme-oxygenase activity; at high concentrations it inhibits it, thus disordering heme metabolism. Both nickel sulfide and sulfate can disrupt immune function by depressing natural killer cell and CD4 lymphocyte populations in blood. Nickel salts at low concentrations can also suppress the natural oxidant cascade following the respiratory burst in phagocytes.
Typically, most absorbed nickel is of dietary origin; hydrogenated oils, cocoa and chocolate are notable sources. Cigarette smoke, plumes from fossil-fuel fired power plants, exhaust from diesel engines and some catalytic converters on engine exhaust systems provide airborne nickel. Batteries (nickel-cadmium), nonprecious dental materials, costume jewelry, and nickel-plated hardware are other sources that may be of concern in nickel dermatitis. Smelting and refining of metal ores and electroplating also add nickel to the environment.
Tin
is above the reference range. Dietary intake of this element can be quite variable, leading to considerable day-to-day differences in urine levels. Elemental, inorganic (two oxidation states, +2 or stannous, and +4 or stannic) and organic forms exist. Organic tin can be dermally absorbed. Elemental tin is very poorly absorbed from the GI tract, and inorganic tin salts are only about 5% absorbed (stannous better than stannic). Short-chain alkyl tins and organo-inorganic salt forms (e.g. triethyltin chloride) are well absorbed. Excretion also depends upon form. Absorbed inorganic tins are at least 85% excreted via urine, with bile handling the remainder. Organic forms are split between urine and bile with relative amounts depending on the organic component. The biological half-time of inorganic tin in the body is about 100 days, while organic tins vary in their tissue residence times. Administration of sulfhydryl (-SH) bearing detoxification agents lessens the toxic effects of organic tin and increases both urine and bile excretion.
Oral ingestion of elemental tin or inorganic forms requires large doses, on the order of 500 mg/kg continuously, to produce toxicity. However, organic tins and organo-inorganic forms can be highly toxic in small doses. Trialkyl tins cause cerebral edema and encephalopathy. Headaches, visual defects and abnormal EEGs have been noted following industrial exposures. Depletion of adrenal catecholamines, hyperglycemia, and uncoupling of cellular oxidative phosphorylation are other effects. Organic tins can also cause immune dysregulation and suppression by affecting lymphatic tissue and T-lymphocytes. Chronic exposure to dialkyltin damages liver cells and the bile duct; and trialkyltin damages the kidneys.
Most encountered tin sources are elemental or inorganic salts for which toxicity is low: tin from tin cans with damaged polymer coatings, stannous fluoride in toothpaste, food, and drinking water exposed to bronze, brass or tin-containing solders. Anti-corrosion electroplating of metals, pewter (tin, antimony, and copper), printer's type, dental amalgams, glazes and pigments, and plastics are other potential sources of inorganic tin. Of more concern are the potential sources of organic or organo-inorganic tins. These include: rodent poisons, fungicides, marine antifouling additives to paints and coatings, wood preservative, herbicide manufacture ("Chloromben"), and acaricides (mite or tick sprays, such as cyhexatin and fenbutatin oxide) used agriculturally on almonds, hops, apples, citrus, peaches, pears, nectarines and plums.
Zinc
is above the reference range. A nutritionally essential element, zinc is needed as an activator for digestive peptidases, alcohol dehydrogenase, alkaline phosphatase, carbonic anhydrase, RNA and DNA polymerases, pyridoxal kinase, and other enzymes in human tissues. Most absorbed zinc is normally disposed of via bile/feces with a lesser and relatively constant degree in urine. Overuse or abuse of zinc-containing nutritional supplements may also increase urinary zinc.
Zinc's toxicity, at high body burdens, apparently is due to displacement of copper and inhibition of membrane ATPase, leading to disrupted sodium and potassium ion transport. Hyperglycemia, hypercholesterolemia, decreased heme synthesis, and decreased albumin/globulin ratio in serum can occur. Zinc "fume fever", from industrial exposure to freshly-formed zinc vapor, produces chills and fever, muscle weakness, fatigue and profuse sweating, usually for 24 to 48 hours following the exposure.
High urine zinc is not attributable to normal dietary sources and is usually the result of excessive use of nutritional supplements, malignancy, industrial exposure, or detoxification treatments, especially with EDTA. Habitual use of galvanized containers for drinking water is a rare cause of zinc excess.
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POST 13.05 
pre-provocation
post-provocation
analysis
reference range
